ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12618001858280

Ethics application status

Approved

Date submitted

5/11/2018

Date registered

15/11/2018

Date last updated

7/04/2024

Date data sharing statement initially provided

15/11/2018

Type of registration

Prospectively registered

Titles & IDs

Public title

Can Heart attack patients without coronary artery blockages benefit from standard heart attack medical treatment strategies?

Scientific title

Randomized Evaluation of Beta Blocker and Angiotensin Converting Enzyme Inhibitor (ACEI) /Angiotensin Receptor Blocker (ARB) Treatment in MINOCA Patients.

Secondary ID [1]

NCT03686696

Secondary ID [2]

EudraCT number 2018-000889-11

Universal Trial Number (UTN)

Trial acronym

MINOCA-BAT

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Myocardial Infarction With Non-obstructive Coronary Arteries

Condition category

Condition code

Cardiovascular

Coronary heart disease

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

The specific brand of medication to be prescribed will be at the discretion of your cardiologist, but the type of drug will be a beta blocker, Angiotensin Converting Enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB). In Australia, commonly prescribed agents in these drug classes include atenolol, perindopril and candesartan.

The randomisation will be carried out using an online randomization module. Following the screening process, the investigator will discuss the suitability of the participant in the trial with the treating cardiologist. Following the approval from the treating cardiologist, the participant will be approached and consented for the trial. The randomization will be performed in the module using permuted block randomization with 1:1:1:1 ratio, stratified by country.

Group 1: Beta Blocker Alone (oral administration)
- Starting dose (first 2 weeks after the randomisation): Atenolol 25mg daily
- Target dose: Atenolol 50 mg daily

Group 2: ACEI or ARB Alone (oral administration)
- Starting dose (first 2 weeks after the randomisation): Perindopril Arginine 2.5mg daily (or alternatively Perindopril Erbumine 2mg daily) or Candesartan 4mg daily
- Target dose: Perindopril Arginine 10 mg daily (or alternatively Perindopril Erbumine 8 mg daily) or Candesartan 16mg daily

Group 3: Both Beta blocker and ACEI or ARB (oral administration)
- Starting dose (first 2 weeks after the randomisation): Atenolol 25mg daily + Perindopril Arginine 2.5mg daily (or alternative ACEI or
ARB as above)
- Target dose: Atenolol 50mg daily + Perindopril Arginine 10 mg daily (or alternative ACEI or ARB as above)

The suggested target dose escalation is at the treating physician's discretion.

Patients will be encouraged to continue the use of the randomized treatment following
discharge for the total study period (4 years) until contraindications.

Due to the pragmatic nature of this trial, the participant's compliance will be evaluated via follow-up telephone calls by the study coordinator. The study medications will be prescribed by the treating clinician, who will have a thorough understanding of the clinical trial, as part of their routine patient care. Participants will be asked to send their pharmacy receipts for the study drugs to the coordinating centre which will also provide an indication as to medication compliance

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

No Intervention: Participants will not be randomised to either beta blockers and/or ACEI/ARB treatments.

Control group

Active

Outcomes

Primary outcome [1]

Time to death of any cause, or time to readmission because of AMI, ischemic stroke or heart failure - A Composite of time to all-cause Death and time to re-admission because of acute myocardial infarction, ischemic stroke or heart failure

1) Death (any cause) will be obtained from the hospital/medical or administrative records.
2) Acute myocardial infarction, ischemic stroke, heart failure, unstable angina, atrial fibrillation
will be obtained from the hospital/medical records and from patient interviews held via telephone.

Timepoint [1]

Time to event from the date of enrollment through study completion, an average of 4 years.

Secondary outcome [1]

Time to All-cause death
Death (any cause) will be obtained from the hospital/medical or administrative records.

Timepoint [1]

Time to event from the date of enrollment through study completion, an average of 4 years.

Secondary outcome [2]

Time to Cardiovascular death

Death (any cause) will be obtained from the hospital/medical or administrative records.

Timepoint [2]

Time to event from the date of enrollment through study completion, an average of 4 years.

Secondary outcome [3]

Time to readmission because of Acute myocardial infarction

Acute myocardial infarction event will be obtained from the hospital/medical records and from patient interviews held via telephone.

Timepoint [3]

Time to event from the date of enrollment through study completion, an average of 4 years.

Secondary outcome [4]

Time to readmission because of ischemic stroke

Stroke event will be obtained from the hospital/medical records and from patient interviews held via telephone.

Timepoint [4]

Time to event from the date of enrollment through study completion, an average of 4 years.

Secondary outcome [5]

Time to readmission because of heart failure

Heart failure event will be obtained from the hospital/medical records and from patient interviews held via telephone.

Timepoint [5]

Time to event from the date of enrollment through study completion, an average of 4 years.

Secondary outcome [6]

Time to Readmission because of unstable angina

Unstable angina event will be obtained from the hospital/medical records and from patient interviews held via telephone.

Timepoint [6]

Time to event from the date of enrollment through study completion, an average of 4 years.

Secondary outcome [7]

Composite of angina frequency, physical limitation, quality of life and patient satisfaction as scored by the Seattle Angina Questionnaire (SAQ)

The SAQ is a self-administered, disease-specific measure for patients with heart disease. The SAQ quantifies patients’ physical limitations caused by angina, the frequency of and recent changes in their symptoms, their satisfaction with treatment, and the degree to which they perceive their disease to affect their quality of life. Each scale is transformed to a score of 0 to 100, where higher scores indicate better function (eg, less physical limitation, less angina, and better quality of life).

Timepoint [7]

1,6, and 12 months post enrollment.
A baseline questionnaire will also be completed at enrolment.

Secondary outcome [8]

Angina frequency scored by SAQ.

Timepoint [8]

1,6, and 12 months post enrollment.
A baseline questionnaire will also be completed at enrolment.

Secondary outcome [9]

Physical limitation scored by SAQ

Timepoint [9]

1,6, and 12 months post enrollment.
A baseline questionnaire will also be completed at enrolment.

Secondary outcome [10]

Quality of life scored by SAQ

Timepoint [10]

1,6, and 12 months post enrollment.
A baseline questionnaire will also be completed at enrolment.

Secondary outcome [11]

Patient satisfaction as scored by the SAQ

Timepoint [11]

1,6, and 12 months post enrollment.
A baseline questionnaire will also be completed at enrolment.

Secondary outcome [12]

Health related quality of life by EQ 5D
EQ-5D is a standardized instrument developed by the EuroQol Group as a measure of health-related quality of life that can be used in a wide range of health conditions and treatments.

Timepoint [12]

1,6, and 12 months post enrollment.
A baseline questionnaire will also be completed at enrolment.

Secondary outcome [13]

Mental health and depression scored by PHQ 9.
The PHQ-9 is a 9-question instrument given to patients in a primary care setting to screen for the presence and severity of depression.

Timepoint [13]

1,6, and 12 months post enrollment.
A baseline questionnaire will also be completed at enrolment.

Secondary outcome [14]

Assess the prevalence of all-cause mortality

Death (any cause) will be obtained from the hospital/medical or administrative records.

Timepoint [14]

12, 24, 36 and 48 months post initial presentation

Secondary outcome [15]

Assess the prevalence of Cardiovascular mortality

Death (any cause) will be obtained from the hospital/medical or administrative records.

Timepoint [15]

12, 24, 36 and 48 months post initial presentation

Secondary outcome [16]

Assess the prevalence of acute myocardial infarction Readmission

The incidence of acute myocardial infarction will be obtained from the hospital/medical records and from patient interviews held via telephone.

Timepoint [16]

12, 24, 36 and 48 months post initial presentation

Secondary outcome [17]

Assess the prevalence of Ischaemic Stroke Admission

The incidence of stroke will be obtained from the hospital/medical records and from patient interviews held via telephone.

Timepoint [17]

12, 24, 36 and 48 months post initial presentation

Secondary outcome [18]

Assess the prevalence of Heart Failure Admission

The incidence of heart failure admission will be obtained from the hospital/medical records and from patient interviews held via telephone.

Timepoint [18]

12, 24, 36 and 48 months post initial presentation

Secondary outcome [19]

Assess the prevalence of Unstable Angina Admission

The incidence of unstable angina will be obtained from the hospital/medical records and from patient interviews held via telephone.

Timepoint [19]

12, 24, 36 and 48 months post initial presentation

Secondary outcome [20]

Time to readmission because of atrial fibrillation.

The incidence of atrial fibrillation admission will be obtained from the hospital/medical records and from patient interviews held via telephone.

Timepoint [20]

Time to event from the date of enrollment through study completion, an average of 4 years.

Eligibility

Key inclusion criteria

1. Age equal or greater than 18 years.
2. A clinical diagnosis of MINOCA, including:
a. Acute myocardial infarction – as per the universal myocardial infarction Criteria (Thygesen et al, 2018)
b. Non-obstructive coronary arteries – no lesion equal or greater than 50% in the potential infarct-related artery.
c. No overt non-ischaemic cause for the acute clinical presentation.
3. Left ventricle ejection fraction equal or less than 40% - assessed by echocardiography, MRI or left ventriculography prior to
randomisation.
4. Written informed consent obtained

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Any condition that may influence the patient's ability to comply with study protocol.
2. Pregnancy
3. Previous revascularization (CABG or PCI)
4. Myocarditis Diagnosis (Cardiac MRI proved myocarditis or a strong clinical suspicion
of myocarditis as a cause of the index event)
5. Clinical signs of heart failure
6. Contraindications for ACEI and ARB
7. Contraindications for beta-blockers
8. Prior use of ACE-I, ARB, or beta blockers, which must continue as per treating
physician
9. New indication for beta-blockers or ACEI/ARB other than as secondary prevention as
per treating physician.
10. Participation in a trial evaluating a drug known to interact with beta blockers or
ACEI/ARB

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Allocation is not concealed.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

The randomization will be performed in the module using permuted block randomization with 1:1:1:1 ratio, stratified by country.

Masking / blinding

Open (masking not used)

Who is / are masked / blinded?

Intervention assignment

Factorial

Other design features

Phase

Phase 4

Type of endpoint/s

Safety/efficacy

Statistical methods / analysis

Data collection and management for all countries will be performed through an electronic data capture system (EDC) located at the UCR, Uppsala, Sweden. Presence of inclusion and/or exclusion criteria and randomized treatment/s including generic substance name and planned target dose will be registered in the patient CRFs. Baseline data, data about in-hospital course and at one-year follow-up will be collected from the CADOSA Registry. Data entered into the online randomisation module at the participating CRF will continuously be collected into a complete study database that will comprise the individual CRF for all patients.

Recruitment

Recruitment status

Stopped early

Data analysis

No data analysis planned

Reason for early stopping/withdrawal

Participant recruitment difficulties

Date of first participant enrolment

Anticipated

1/12/2018

Actual

23/01/2019

Date of last participant enrolment

Anticipated

1/01/2022

Actual

16/11/2021

Date of last data collection

Anticipated

1/01/2026

Actual

31/05/2023

Sample size

Target

3500

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW,QLD,SA,WA,VIC

Recruitment hospital [1]

The Queen Elizabeth Hospital - Woodville

Recruitment hospital [2]

The Royal Adelaide Hospital - Adelaide

Recruitment hospital [3]

Lyell McEwin Hospital - Elizabeth Vale

Recruitment hospital [4]

John Hunter Hospital - New Lambton

Recruitment hospital [5]

Gold Coast Hospital - Southport

Recruitment hospital [6]

Sunshine Hospital - St Albans

Recruitment hospital [7]

Royal Perth Hospital - Perth

Recruitment hospital [8]

Fiona Stanley Hospital - Murdoch

Recruitment hospital [9]

Gosford Hospital - Gosford

Recruitment postcode(s) [1]

5011 - Woodville

Recruitment postcode(s) [2]

5000 - Adelaide

Recruitment postcode(s) [3]

5112 - Elizabeth Vale

Recruitment postcode(s) [4]

2305 - New Lambton

Recruitment postcode(s) [5]

4215 - Southport

Recruitment postcode(s) [6]

3021 - St Albans

Recruitment postcode(s) [7]

6000 - Perth

Recruitment postcode(s) [8]

6150 - Murdoch

Recruitment postcode(s) [9]

2250 - Gosford

Recruitment outside Australia

Country [1]

Sweden

State/province [1]

Uppsala

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

The Hospital Research Foundation

Address [1]

60 Woodville Road
Woodville, SA 5011

Country [1]

Australia

Primary sponsor type

University

Name

The University of Adelaide

Address

Adelaide SA 5005

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Other collaborator category [1]

University

Name [1]

Uppsala university

Address [1]

752 36 Uppsala, Sweden

Country [1]

Sweden

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Central Adelaide Local Health Network Human Research Ethics Committee

Ethics committee address [1]

Level 3, Roma Mitchell House
136 North Terrace
Adelaide, South Australia, 5000

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

12/03/2018

Approval date [1]

14/06/2018

Ethics approval number [1]

HREC/18/CALHN/157

Summary

Brief summary

Myocardial infarction with non-obstructive coronary arteries" (MINOCA) occurs in 5-10% of all patients with acute myocardial infarction (AMI). There are neither any randomized clinical trials in MINOCA patients evaluating effects of secondary preventive treatments proven beneficial in patients with classic AMI, nor any treatment guidelines. The primary objective of this multi-national, multi-center pragmatic randomized clinical trial is to determine whether oral beta-blockade compared to no oral beta-blockade, and whether Angiotensin Converting Enzyme Inhibitors (ACEI/ Angiotensin Receptor Blockers (ARB) compared to no ACEI/ARB, reduce the composite endpoint of death of any cause and readmission because of AMI, ischemic stroke or heart failure in patients discharged with MINOCA and with no clinical signs of heart failure and with left ventricular (LV) systolic ejection fraction above or equal to 40%.

Trial website

http://www.ucr.uu.se/swedeheart/forskning-swedeheart/pagaende-r-rct/minoca-bat

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof John F Beltrame

Address

Queen Elizabeth Hospital Campus
Woodville South, SA 5011

Country

Australia

Phone

+61 88222 6740

Fax

+61 8 8222 6042

[email protected]

Contact person for public queries

Name

Sivabaskari Pasupathy

Address

Faculty of Health Sciences, Medical Specialities
28 Woodville Road
Woodville South SA 5011

Country

Australia

Phone

+61 8 8222 8685

Fax

+61 8 8222 6042

[email protected]

Contact person for scientific queries

Name

John F Beltrame

Address

Queen Elizabeth Hospital Campus
Woodville South, SA 5011

Country

Australia

Phone

+61 88222 6740

Fax

+61 8 8222 6042

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

Yes

What data in particular will be shared?

A limited, de-identified set of data available for researchers outside the primary investigators and will be specified in the data sharing plan.

When will data be available (start and end dates)?

Two years after the publication of the primary results of the study. The endpoint of the availability to be specified by the investigators.

Available to whom?

Researchers outside the primary investigators.

Available for what types of analyses?

The type of analyses must be specified in the data sharing agreement between the providing agency and the requesting researchers.

How or where can data be obtained?

Before data are shared, a data-sharing agreement should be established documenting what data are being shared and how the data can be used. The agreement serves two purposes. First, it protects the agency providing the data, ensuring that the data will not be misused. Second, it prevents miscommunication on the part of the provider of the data and the agency receiving the data by making certain that any questions about data use are discussed. The following items should be covered in the data-sharing agreement:

Period of agreement
The intended use of the data
Constraints on the use of the data
Data confidentiality
Data security
Methods of data-sharing

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
12	Ethical approval					376234-(Uploaded-31-10-2018-14-30-44)-Study-related document.pdf

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

Trial Review

Documents added manually

Documents added automatically